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| | ==Crystal structure of LGG-1 complexed with a WEEL peptide== | | ==Crystal structure of LGG-1 complexed with a WEEL peptide== |
| - | <StructureSection load='5azf' size='340' side='right' caption='[[5azf]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='5azf' size='340' side='right'caption='[[5azf]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5azf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AZF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5azf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AZF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5azg|5azg]], [[5azh|5azh]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5azf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azf OCA], [http://pdbe.org/5azf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5azf RCSB], [http://www.ebi.ac.uk/pdbsum/5azf PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5azf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azf OCA], [https://pdbe.org/5azf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5azf RCSB], [https://www.ebi.ac.uk/pdbsum/5azf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5azf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LGG1_CAEEL LGG1_CAEEL]] Ubiquitin-like modifier involved in autophagy and essential for dauer development and life-span extension (PubMed:12958363, PubMed:20523114). Plays a role in mitophagy (PubMed:25896323).<ref>PMID:12958363</ref> <ref>PMID:20523114</ref> <ref>PMID:25896323</ref> [[http://www.uniprot.org/uniprot/ATG19_YEAST ATG19_YEAST]] Cargo-receptor protein involved in the cytoplasm to vacuole transport (Cvt) and in autophagy. Recognizes cargo proteins, such as APE4, LAP3, LAP4 and AMS1 and delivers them to the pre-autophagosomal structure for eventual engulfment by the autophagosome and targeting to the vacuole. Involved in the organization of the preautophagosomal structure (PAS). ATG19 association with cargo protein is required to localize ATG11 to the PAS. Also involved in endoplasmic reticulum-specific autophagic process, in selective removal of ER-associated degradation (ERAD) substrates, and is essential for the survival of cells subjected to severe ER stress. Plays also a role in regulation of filamentous growth.<ref>PMID:11382752</ref> <ref>PMID:11430817</ref> <ref>PMID:12479807</ref> <ref>PMID:12479808</ref> <ref>PMID:15138258</ref> <ref>PMID:15801807</ref> <ref>PMID:16186126</ref> <ref>PMID:15659643</ref> <ref>PMID:17132049</ref> <ref>PMID:17700056</ref> <ref>PMID:17192412</ref> <ref>PMID:17238920</ref> <ref>PMID:19061865</ref> <ref>PMID:21228276</ref> <ref>PMID:19021777</ref> <ref>PMID:20659891</ref> | + | [https://www.uniprot.org/uniprot/LGG1_CAEEL LGG1_CAEEL] Ubiquitin-like modifier involved in autophagy and essential for dauer development and life-span extension (PubMed:12958363, PubMed:20523114). Plays a role in mitophagy (PubMed:25896323).<ref>PMID:12958363</ref> <ref>PMID:20523114</ref> <ref>PMID:25896323</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development. |
| | + | |
| | + | Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.,Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H Mol Cell. 2015 Dec 17;60(6):914-29. doi: 10.1016/j.molcel.2015.11.019. PMID:26687600<ref>PMID:26687600</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5azf" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Noda, N N]] | + | [[Category: Caenorhabditis elegans]] |
| - | [[Category: Watanabe, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Autophagy]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Protein binding]] | + | [[Category: Noda NN]] |
| - | [[Category: Ubiquitin-like]] | + | [[Category: Watanabe Y]] |
| Structural highlights
Function
LGG1_CAEEL Ubiquitin-like modifier involved in autophagy and essential for dauer development and life-span extension (PubMed:12958363, PubMed:20523114). Plays a role in mitophagy (PubMed:25896323).[1] [2] [3]
Publication Abstract from PubMed
Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.
Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.,Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H Mol Cell. 2015 Dec 17;60(6):914-29. doi: 10.1016/j.molcel.2015.11.019. PMID:26687600[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003 Sep 5;301(5638):1387-91. PMID:12958363 doi:http://dx.doi.org/10.1126/science.1087782
- ↑ Alberti A, Michelet X, Djeddi A, Legouis R. The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. Autophagy. 2010 Jul;6(5):622-33. doi: 10.4161/auto.6.5.12252. Epub 2010 Jul 1. PMID:20523114 doi:http://dx.doi.org/10.4161/auto.6.5.12252
- ↑ Palikaras K, Lionaki E, Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature. 2015 May 28;521(7553):525-8. doi: 10.1038/nature14300. Epub 2015 Apr 20. PMID:25896323 doi:http://dx.doi.org/10.1038/nature14300
- ↑ Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H. Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. Mol Cell. 2015 Dec 17;60(6):914-29. doi: 10.1016/j.molcel.2015.11.019. PMID:26687600 doi:http://dx.doi.org/10.1016/j.molcel.2015.11.019
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